- PROJECT 1 Presently, there can be considerable uncertainty in the clinical diagnosis of the common neurodegenerative pathological dementia syndromes [AD, LBD and FTD] antemortem because of clinical heterogeneity (wherein the dementia underlying pathology does not match the clinical syndrome), subtle symptoms early in the disease process, and frequent occurrence of mixed dementias. The central aim of this proposal is to develop a methodology that uses the wealth of clinical, imaging and pathology data collected in past and current ADRC funding cycles to improve the antemortem prediction of the dementia pathology and long-term clinical outcomes in new incoming patients. Our working hypothesis is that an individual subject's cognitive performance can be approximately modeled based on the subjects multi-modal imaging scans which are surrogates of pathology, cognitive reserve, MRI evidence of CVD and demographics. Based on this hypothesis, we plan to integrate clinical, pathology and imaging information on about 370+ demented patients with autopsy diagnosis and at least one imaging exam available before death from the past and current ADRC cycles and use this information for diagnosis and prognosis of new incoming patients. The overall methodology which we will create will operate as follows: 1) identify the patients (matched subjects) in our database who match the new incoming patient based on the multi-modal images, cognitive reserve, vascular disease and demographics and 2) use the matched subjects to aid in the diagnosis and prognosis of the new patient.